Journal of Computer-Aided Molecular Design

, Volume 24, Issue 5, pp 423–431 | Cite as

Computational studies on the interaction of ABO-active saccharides with the norovirus VA387 capsid protein can explain experimental binding data

  • Chaitanya A. K. Koppisetty
  • Waqas Nasir
  • Francesco Strino
  • Gustaf E. Rydell
  • Göran Larson
  • Per-Georg NyholmEmail author


Norovirus strains are known to cause recurring epidemics of winter vomiting disease. The crystal structure of the capsid protein of VA387, a representative of the clinically important GII.4 genocluster, was recently solved in complex with histo-blood group A- and B-trisaccharides. However, the VA387 strain is known to bind also to other natural carbohydrates for which detailed structural information of the complexes is not available. In this study we have computationally explored the fit of the VA387 with a set of naturally occurring carbohydrate ligands containing a terminal α1,2-linked fucose. MD simulations both with explicit and implicit solvent models indicate that type 1 and 3 extensions of the ABO-determinant including ALeb and BLeb pentasaccharides can be well accommodated in the site. Scoring with Glide XP indicates that the downstream extensions of the ABO-determinants give an increase in binding strength, although the α1,2-linked fucose is the single strongest interacting residue. An error was discovered in the geometry of the GalNAc-Gal moiety of the published crystal structure of the A-trisaccharide/VA387 complex. The present modeling of the complexes with histo-blood group A-active structures shows some contacts which provide insight into mutational data, explaining the involvement of I389 and Q331. Our results can be applicable in structure-based design of adhesion inhibitors of noroviruses.


Norovirus Blood group determinants ABO-saccharides Molecular docking Molecular dynamics 



Grants from the Swedish research council (8266) and from governmental funds to the Sahlgrenska University Hospital and financial support from Biognos AB, Göteborg, are gratefully acknowledged. We are grateful for valuable discussions with Drs. I. Pascher, S. Sundell and G. Kemp.

Supplementary material

10822_2010_9353_MOESM1_ESM.doc (4.3 mb)
Supplementary material 1 (DOC 4445 kb)


  1. 1.
    Atmar RL, Estes MK (2006) Gastroenterol Clin North Am 35(2):275CrossRefGoogle Scholar
  2. 2.
    Hutson AM, Airaud F, LePendu J, Estes MK, Atmar RL (2005) J Med Virol 77(1):116CrossRefGoogle Scholar
  3. 3.
    Lindesmith L, Moe C, Marionneau S, Ruvoen N, Jiang X, Lindblad L, Stewart P, LePendu J, Baric R (2003) Nat Med 9(5):548CrossRefGoogle Scholar
  4. 4.
    Kindberg E, Akerlind B, Johnsen C, Knudsen JD, Heltberg O, Larson G, Bottiger B, Svensson L (2007) J Clin Microbiol 45(8):2720CrossRefGoogle Scholar
  5. 5.
    Tan M, Jin M, Xie H, Duan Z, Jiang X, Fang Z (2008) J Med Virol 80(7):1296CrossRefGoogle Scholar
  6. 6.
    Thorven M, Grahn A, Hedlund KO, Johansson H, Wahlfrid C, Larson G, Svensson L (2005) J Virol 79(24):15351CrossRefGoogle Scholar
  7. 7.
    Larsson MM, Rydell GE, Grahn A, Rodriguez-Diaz J, Akerlind B, Hutson AM, Estes MK, Larson G, Svensson L (2006) J Infect Dis 194(10):1422CrossRefGoogle Scholar
  8. 8.
    Huang P, Farkas T, Zhong W, Tan M, Thornton S, Morrow AL, Jiang X (2005) J Virol 79(11):6714CrossRefGoogle Scholar
  9. 9.
    Marionneau S, Ruvoen N, Le Moullac-Vaidye B, Clement M, Cailleau-Thomas A, Ruiz-Palacois G, Huang P, Jiang X, Le Pendu J (2002) Gastroenterology 122(7):1967CrossRefGoogle Scholar
  10. 10.
    Harrington PR, Vinje J, Moe CL, Baric RS (2004) J Virol 78(6):3035CrossRefGoogle Scholar
  11. 11.
    Harrington PR, Lindesmith L, Yount B, Moe CL, Baric RS (2002) J Virol 76(23):12335CrossRefGoogle Scholar
  12. 12.
    Kelly RJ, Rouquier S, Giorgi D, Lennon GG, Lowe JB (1995) J Biol Chem 270(9):4640CrossRefGoogle Scholar
  13. 13.
    Choi JM, Hutson AM, Estes MK, Prasad BV (2008) Proc Natl Acad Sci U S A 105(27):9175CrossRefGoogle Scholar
  14. 14.
    Bu W, Mamedova A, Tan M, Xia M, Jiang X, Hegde RS (2008) J Virol 82(11):5340CrossRefGoogle Scholar
  15. 15.
    Cao S, Lou Z, Tan M, Chen Y, Liu Y, Zhang Z, Zhang XC, Jiang X, Li X, Rao Z (2007) J Virol 81(11):5949CrossRefGoogle Scholar
  16. 16.
    Tan M, Xia M, Cao S, Huang P, Farkas T, Meller J, Hegde RS, Li X, Rao Z, Jiang X (2008) Virology 379(2):324CrossRefGoogle Scholar
  17. 17.
    Rydell GE, Nilsson J, Rodriguez-Diaz J, Ruvoen-Clouet N, Svensson L, Le Pendu J, Larson G (2009) Glycobiology 19(3):309CrossRefGoogle Scholar
  18. 18.
    Lindesmith LC, Donaldson EF, Lobue AD, Cannon JL, Zheng DP, Vinje J, Baric RS (2008) PLoS Med 5(2):e31CrossRefGoogle Scholar
  19. 19.
    Shirato H, Ogawa S, Ito H, Sato T, Kameyama A, Narimatsu H, Xiaofan Z, Miyamura T, Wakita T, Ishii K, Takeda N (2008) J Virol 82(21):10756CrossRefGoogle Scholar
  20. 20.
    Siebenga JJ, Vennema H, Zheng DP, Vinje J, Lee BE, Pang XL, Ho EC, Lim W, Choudekar A, Broor S, Halperin T, Rasool NB, Hewitt J, Greening GE, Jin M, Duan ZJ, Lucero Y, O’Ryan M, Hoehne M, Schreier E, Ratcliff RM, White PA, Iritani N, Reuter G, Koopmans M (2009) J Infect Dis 200(5):802CrossRefGoogle Scholar
  21. 21.
    Bohne A, Lang E, von der Lieth CW (1999) Bioinformatics 15(9):767CrossRefGoogle Scholar
  22. 22.
    Lii J-H, Chen K-H, Allinger NL (2003) J Comput Chem 24(12):1504CrossRefGoogle Scholar
  23. 23.
    Nahmany A, Strino F, Rosen J, Kemp GJL, Nyholm P-G (2005) Carbohydr Res 340(5):1059CrossRefGoogle Scholar
  24. 24.
    Strino F, Lii J-H, Gabius H-J, Nyholm P-G (2009) J Comput Aided Mol Des 23(12):845CrossRefGoogle Scholar
  25. 25.
    Agostino M, Jene C, Boyle T, Ramsland PA, Yuriev E (2009) J Chem Inf Model 49(12):2749CrossRefGoogle Scholar
  26. 26.
    Nurisso A, Kozmon S, Imberty A (2008) Mol Simul 34(4):469CrossRefGoogle Scholar
  27. 27.
    Stortz CA, Johnson GP, French AD, Csonka GI (2009) Carbohydr Res 344(16):2217CrossRefGoogle Scholar
  28. 28.
    Kirschner KN, Yongye AB, Tschampel SM, Gonzalez-Outeirino J, Daniels CR, Foley BL, Woods RJ (2008) J Comput Chem 29(4):622CrossRefGoogle Scholar
  29. 29.
    Hornak V, Abel R, Okur A, Strockbine B, Roitberg A, Simmerling C (2006) Proteins 65(3):712CrossRefGoogle Scholar
  30. 30.
    Onufriev A, Bashford D, Case DA (2004) Proteins 55(2):383CrossRefGoogle Scholar
  31. 31.
    Carlsson B, Kindberg E, Buesa J, Rydell GE, Lidon MF, Montava R, Abu Mallouh R, Grahn A, Rodriguez-Diaz J, Bellido J, Arnedo A, Larson G, Svensson L (2009) PLoS One 4(5):e5593CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Chaitanya A. K. Koppisetty
    • 1
    • 2
  • Waqas Nasir
    • 2
    • 3
  • Francesco Strino
    • 1
    • 3
  • Gustaf E. Rydell
    • 4
  • Göran Larson
    • 4
  • Per-Georg Nyholm
    • 1
    • 3
    Email author
  1. 1.Biognos ABGothenburgSweden
  2. 2.Department of Computer Science and EngineeringChalmers University of TechnologyGothenburgSweden
  3. 3.Institute of BiomedicineUniversity of GothenburgGothenburgSweden
  4. 4.Department of Clinical Chemistry and Transfusion MedicineSahlgrenska University HospitalGothenburgSweden

Personalised recommendations